Advertisement

Granulomatosis with Polyangiitis

  • Christian PagnouxEmail author
Chapter
Part of the Rare Diseases of the Immune System book series (RDIS)

Abstract

Granulomatosis with polyangiitis (GPA) is a small-vessel necrotizing vasculitis that most characteristically affects the ear, nose, and throat (ENT), lungs, and/or kidneys. The median age at diagnosis is in the fifth decade, but children and older people can be affected. GPA origin remains unknown, although knowledge of the main pathogenic mechanisms has greatly improved, particularly since the discovery of antineutrophil cytoplasmic antibodies (ANCA) in 1985. GPA is typically associated with the presence in serum of these autoantibodies, mainly cANCA by indirect immunofluorescence, directed against proteinase 3 (PR3) on ELISA. However, some patients are ANCA-negative, especially those with “limited” disease forms, and some are positive for pANCA, directed against myeloperoxidase (MPO) on ELISA. In the mid-1950s, the median survival of GPA patients was only 5 months, with 82% of deaths occurring within 1 year of the first symptoms. With current treatments, which include first an induction phase, based on the combination of corticosteroids and an immunosuppressant, then a maintenance treatment phase, remission can be achieved in more than 80% of cases. However, the relapse-free survival rate does not exceed 42–57% at 5 years with conventional maintenance treatments, whose optimal duration is still unclear. Biological marker(s) to reliably monitor disease activity and predict outcomes may finally be identified, and new potential therapeutic targets are being developed at an increasing pace.

Keywords

Granulomatosis with polyangiitis ANCA-associated vasculitis Alveolar hemorrhage Pauci-immune glomerulonephritis Cyclophosphamide Rituximab Plasma exchange 

References

  1. 1.
    Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65:1–11.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Jennette JC, Falk RJ, Andrassy K, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum. 1994;37:187–92.CrossRefGoogle Scholar
  3. 3.
    Mohammad AJ, Jacobsson LT, Westman KW, Sturfelt G, Segelmark M. Incidence and survival rates in Wegener’s granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and polyarteritis nodosa. Rheumatology (Oxford). 2009;48:1560–5.CrossRefGoogle Scholar
  4. 4.
    Watts RA, Mahr A, Mohammad AJ, Gatenby P, Basu N, Flores-Suarez LF. Classification, epidemiology and clinical subgrouping of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Nephrol Dial Transplant. 2015;30(Suppl 1):i14–22.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992;116:488–98.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Holle JU, Gross WL, Latza U, et al. Improved outcome in 445 patients with Wegener’s granulomatosis in a German vasculitis center over four decades. Arthritis Rheum. 2011;63:257–66.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Jennette JC, Falk RJ, Gasim AH. Pathogenesis of antineutrophil cytoplasmic autoantibody vasculitis. Curr Opin Nephrol Hypertens. 2011;20:263–70.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Walton EW. Giant-cell granuloma of the respiratory tract (Wegener’s granulomatosis). Br Med J. 1958;2:265–70.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Wallace ZS, Lu N, Unizony S, Stone JH, Choi HK. Improved survival in granulomatosis with polyangiitis: a general population-based study. Semin Arthritis Rheum. 2016;45:483–9.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Flossmann O, Berden A, de Groot K, et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis. 2011;70:488–94.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Yates M, Watts RA, Bajema IM, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016;75:1583–94.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    McGeoch L, Twilt M, Famorca L, et al. CanVasc Recommendations for the Management of Antineutrophil Cytoplasm Antibody-associated Vasculitides. J Rheumatol. 2016;43:97–120.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Mahr AD. Epidemiological features of Wegener’s granulomatosis and microscopic polyangiitis: two diseases or one ‘anti-neutrophil cytoplasm antibodies-associated vasculitis’ entity? APMIS Suppl. 2009;(127):41–7.CrossRefGoogle Scholar
  14. 14.
    Mohammad AJ, Jacobsson LT, Mahr AD, Sturfelt G, Segelmark M. Prevalence of Wegener’s granulomatosis, microscopic polyangiitis, polyarteritis nodosa and Churg-Strauss syndrome within a defined population in southern Sweden. Rheumatology (Oxford). 2007;46:1329–37.CrossRefGoogle Scholar
  15. 15.
    Abdou NI, Kullman GJ, Hoffman GS, et al. Wegener’s granulomatosis: survey of 701 patients in North America. Changes in outcome in the 1990s. J Rheumatol. 2002;29:309–16.PubMedGoogle Scholar
  16. 16.
    Koldingsnes W, Nossent H. Epidemiology of Wegener’s granulomatosis in northern Norway. Arthritis Rheum. 2000;43:2481–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Takala JH, Kautiainen H, Malmberg H, Leirisalo-Repo M. Incidence of Wegener’s granulomatosis in Finland 1981-2000. Clin Exp Rheumatol. 2008;26:S81–5.PubMedGoogle Scholar
  18. 18.
    Watts RA, Al-Taiar A, Scott DG, Macgregor AJ. Prevalence and incidence of Wegener’s granulomatosis in the UK general practice research database. Arthritis Rheum. 2009;61:1412–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Watts RA, Mooney J, Skinner J, Scott DG, Macgregor AJ. The contrasting epidemiology of granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis. Rheumatology (Oxford). 2012;51:926–31.CrossRefGoogle Scholar
  20. 20.
    Lane SE, Watts R, Scott DG. Epidemiology of systemic vasculitis. Curr Rheumatol Rep. 2005;7:270–5.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    van Timmeren MM, Heeringa P. Pathogenesis of ANCA-associated vasculitis: recent insights from animal models. Curr Opin Rheumatol. 2012;24:8–14.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Jennette JC, Falk RJ. Pathogenesis of antineutrophil cytoplasmic autoantibody-mediated disease. Nat Rev Rheumatol. 2014;10:463–73.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Pendergraft WF III, Pressler BM, Jennette JC, Falk RJ, Preston GA. Autoantigen complementarity: a new theory implicating complementary proteins as initiators of autoimmune disease. J Mol Med (Berl). 2005;83:12–25.CrossRefGoogle Scholar
  24. 24.
    Stegeman CA, Tervaert JW, Sluiter WJ, Manson WL, de Jong PE, Kallenberg CG. Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis. Ann Intern Med. 1994;120:12–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Knight A, Sandin S, Askling J. Increased risk of autoimmune disease in families with Wegener’s granulomatosis. J Rheumatol. 2010;37:2553–8.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Jagiello P, Gross WL, Epplen JT. Complex genetics of Wegener granulomatosis. Autoimmun Rev. 2005;4:42–7.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Wieczorek S, Holle JU, Epplen JT. Recent progress in the genetics of Wegener’s granulomatosis and Churg-Strauss syndrome. Curr Opin Rheumatol. 2010;22:8–14.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Lyons PA, Rayner TF, Trivedi S, et al. Genetically distinct subsets within ANCA-associated vasculitis. N Engl J Med. 2012;367:214–23.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Rahmattulla C, Mooyaart AL, van Hooven D, et al. Genetic variants in ANCA-associated vasculitis: a meta-analysis. Ann Rheum Dis. 2016;75:1687–92.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Hong Y, Eleftheriou D, Hussain AA, et al. Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles. J Am Soc Nephrol. 2012;23:49–62.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Kessenbrock K, Krumbholz M, Schonermarck U, et al. Netting neutrophils in autoimmune small-vessel vasculitis. Nat Med. 2009;15:623–5.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Kraaij T, Kamerling SWA, van Dam LS, et al. Excessive neutrophil extracellular trap formation in ANCA-associated vasculitis is independent of ANCA. Kidney Int. 2018;94:139.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Xiao H, Heeringa P, Hu P, et al. Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J Clin Invest. 2002;110:955–63.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Abdulahad WH, Stegeman CA, Limburg PC, Kallenberg CG. CD4-positive effector memory T cells participate in disease expression in ANCA-associated vasculitis. Ann N Y Acad Sci. 2007;1107:22–31.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Abdulahad WH, Stegeman CA, van der Geld YM, Doornbos-van der Meer B, Limburg PC, Kallenberg CG. Functional defect of circulating regulatory CD4+ T cells in patients with Wegener’s granulomatosis in remission. Arthritis Rheum. 2007;56:2080–91.CrossRefGoogle Scholar
  36. 36.
    Regent A, Lofek S, Dib H, et al. Identification of target antigens of anti-endothelial cell antibodies in patients with anti-neutrophil cytoplasmic antibody-associated vasculitides: a proteomic approach. Clin Immunol. 2014;153:123–35.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Holmen C, Elsheikh E, Christensson M, et al. Anti endothelial cell autoantibodies selectively activate SAPK/JNK signalling in Wegener’s granulomatosis. J Am Soc Nephrol. 2007;18:2497–508.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Popa ER, Franssen CF, Limburg PC, Huitema MG, Kallenberg CG, Tervaert JW. In vitro cytokine production and proliferation of T cells from patients with anti-proteinase 3- and antimyeloperoxidase-associated vasculitis, in response to proteinase 3 and myeloperoxidase. Arthritis Rheum. 2002;46:1894–904.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Abdulahad WH, Stegeman CA, Limburg PC, Kallenberg CG. Skewed distribution of Th17 lymphocytes in patients with Wegener’s granulomatosis in remission. Arthritis Rheum. 2008;58:2196–205.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Stone JH. Limited versus severe Wegener’s granulomatosis: baseline data on patients in the Wegener’s granulomatosis etanercept trial. Arthritis Rheum. 2003;48:2299–309.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Solans-Laque R, Fraile G, Rodriguez-Carballeira M, et al. Clinical characteristics and outcome of Spanish patients with ANCA-associated vasculitides: impact of the vasculitis type, ANCA specificity, and treatment on mortality and morbidity. Medicine (Baltimore). 2017;96:e6083.CrossRefGoogle Scholar
  42. 42.
    Reinhold-Keller E, Beuge N, Latza U, et al. An interdisciplinary approach to the care of patients with Wegener’s granulomatosis: long-term outcome in 155 patients. Arthritis Rheum. 2000;43:1021–32.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Pagnoux C, Wolter NE. Vasculitis of the upper airways. Swiss Med Wkly. 2012;142:w13541.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Fasunla JA, Hundt W, Lutz J, Forger F, Thurmel K, Steinbach S. Evaluation of smell and taste in patients with Wegener’s granulomatosis. Eur Arch Otorhinolaryngol. 2012;269:179–86.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Martinez Del Pero M, Walsh M, Luqmani R, et al. Long-term damage to the ENT system in Wegener’s granulomatosis. Eur Arch Otorhinolaryngol. 2011;268:733–9.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Langford CA, Sneller MC, Hallahan CW, et al. Clinical features and therapeutic management of subglottic stenosis in patients with Wegener’s granulomatosis. Arthritis Rheum. 1996;39:1754–60.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Terrier B, Dechartres A, Girard C, et al. Granulomatosis with polyangiitis: endoscopic management of tracheobronchial stenosis: results from a multicentre experience. Rheumatology (Oxford). 2015;54:1852–7.CrossRefGoogle Scholar
  48. 48.
    Russell BA, Mohan S, Chahal R, Carette S, Pagnoux C, Canadian Vasculitis N. Prognostic significance of cavitary lung nodules in granulomatosis with polyangiitis - a clinical and imaging study of 225 patients. Arthritis Care Res. 2018;70:1082.CrossRefGoogle Scholar
  49. 49.
    Girard C, Charles P, Terrier B, et al. Tracheobronchial stenoses in granulomatosis with polyangiitis (Wegener’s): a report on 26 cases. Medicine (Baltimore). 2015;94:e1088.CrossRefGoogle Scholar
  50. 50.
    Berden AE, Ferrario F, Hagen EC, et al. Histopathologic classification of ANCA-associated glomerulonephritis. J Am Soc Nephrol. 2010;21:1628–36.CrossRefGoogle Scholar
  51. 51.
    Pagnoux C, Guillevin L. Peripheral neuropathy in systemic vasculitides. Curr Opin Rheumatol. 2005;17:41–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Nishino H, Rubino FA, DeRemee RA, Swanson JW, Parisi JE. Neurological involvement in Wegener’s granulomatosis: an analysis of 324 consecutive patients at the Mayo Clinic. Ann Neurol. 1993;33:4–9.PubMedCrossRefGoogle Scholar
  53. 53.
    de Groot K, Schmidt DK, Arlt AC, Gross WL, Reinhold-Keller E. Standardized neurologic evaluations of 128 patients with Wegener granulomatosis. Arch Neurol. 2001;58:1215–21.CrossRefGoogle Scholar
  54. 54.
    De Luna G, Terrier B, Kaminsky P, et al. Central nervous system involvement of granulomatosis with polyangiitis: clinical-radiological presentation distinguishes different outcomes. Rheumatology (Oxford). 2015;54:424–32.CrossRefGoogle Scholar
  55. 55.
    Younger DS. Vasculitis of the nervous system. Curr Opin Neurol. 2004;17:317–36.PubMedCrossRefGoogle Scholar
  56. 56.
    Goyal M, Kucharczyk W, Keystone E. Granulomatous hypophysitis due to Wegener’s granulomatosis. AJNR Am J Neuroradiol. 2000;21:1466–9.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Frances C, Du LT, Piette JC, et al. Wegener’s granulomatosis. Dermatological manifestations in 75 cases with clinicopathologic correlation. Arch Dermatol. 1994;130:861–7.PubMedCrossRefGoogle Scholar
  58. 58.
    Le Hello C, Bonte I, Mora JJ, Verneuil L, Noel LH, Guillevin L. Pyoderma gangrenosum associated with Wegener’s granulomatosis: partial response to mycophenolate mofetil. Rheumatology (Oxford). 2002;41:236–7.CrossRefGoogle Scholar
  59. 59.
    Rothschild PR, Pagnoux C, Seror R, Brezin AP, Delair E, Guillevin L. Ophthalmologic manifestations of systemic necrotizing vasculitides at diagnosis: a retrospective study of 1286 patients and review of the literature. Semin Arthritis Rheum. 2013;42:507–14.PubMedCrossRefGoogle Scholar
  60. 60.
    McGeoch L, Carette S, Cuthbertson D, et al. Cardiac Involvement in Granulomatosis with Polyangiitis. J Rheumatol. 2015;42:1209–12.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Morelli S, Gurgo Di Castelmenardo AM, Conti F, et al. Cardiac involvement in patients with Wegener’s granulomatosis. Rheumatol Int. 2000;19:209–12.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Mavrogeni S, Schwitter J, van Rossum A, et al. Cardiac magnetic resonance imaging in myocardial inflammation in autoimmune rheumatic diseases: an appraisal of the diagnostic strengths and limitations of the Lake Louise criteria. Int J Cardiol. 2018;252:216–9.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Pugnet G, Gouya H, Puechal X, et al. Cardiac involvement in granulomatosis with polyangiitis: a magnetic resonance imaging study of 31 consecutive patients. Rheumatology (Oxford). 2017;56:947–56.CrossRefGoogle Scholar
  64. 64.
    Pagnoux C, Mahr A, Cohen P, Guillevin L. Presentation and outcome of gastrointestinal involvement in systemic necrotizing vasculitides: analysis of 62 patients with polyarteritis nodosa, microscopic polyangiitis, Wegener granulomatosis, Churg-Strauss syndrome, or rheumatoid arthritis-associated vasculitis. Medicine (Baltimore). 2005;84:115–28.CrossRefGoogle Scholar
  65. 65.
    Soowamber M, Weizman AV, Pagnoux C. Gastrointestinal aspects of vasculitides. Nat Rev Gastroenterol Hepatol. 2017;14:185–94.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Sy A, Khalidi N, Dehghan N, et al. Vasculitis in patients with inflammatory bowel diseases: a study of 32 patients and systematic review of the literature. Semin Arthritis Rheum. 2016;45:475–82.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Gal AA, Masor JJ. Splenic involvement in Wegener’s granulomatosis. Arch Pathol Lab Med. 1996;120:974–7.PubMedPubMedCentralGoogle Scholar
  68. 68.
    McCain M, Quinet R, Davis W, et al. Splenic rupture as the presenting manifestation of vasculitis. Semin Arthritis Rheum. 2002;31:311–6.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Arlet JB, Le Thi Huong D, Marinho A, Cluzel P, Wechsler B, Piette JC. Arterial aneurysms in Wegener’s granulomatosis: case report and literature review. Semin Arthritis Rheum. 2008;37:265–8.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Lie JT. Wegener’s granulomatosis: histological documentation of common and uncommon manifestations in 216 patients. Vasa. 1997;26:261–70.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Barreto P, Pagnoux C, Luca L, et al. Dorsal prevertebral lesions in Wegener granulomatosis: report on four cases. Joint Bone Spine. 2011;78:88–91.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Merkel PA, Lo GH, Holbrook JT, et al. Brief communication: high incidence of venous thrombotic events among patients with Wegener granulomatosis: the Wegener’s Clinical Occurrence of Thrombosis (WeCLOT) Study. Ann Intern Med. 2005;142:620–6.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Allenbach Y, Seror R, Pagnoux C, Teixeira L, Guilpain P, Guillevin L. High frequency of venous thromboembolic events in Churg-Strauss syndrome, Wegener’s granulomatosis and microscopic polyangiitis but not polyarteritis nodosa: a systematic retrospective study on 1130 patients. Ann Rheum Dis. 2009;68:564–7.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Kronbichler A, Leierer J, Leierer G, et al. Clinical associations with venous thromboembolism in anti-neutrophil cytoplasm antibody-associated vasculitides. Rheumatology (Oxford). 2017;56:704–8.Google Scholar
  75. 75.
    Berti A, Matteson EL, Crowson CS, Specks U, Cornec D. Risk of Cardiovascular disease and venous thromboembolism among patients with incident ANCA-associated vasculitis: a 20-year population-based cohort study. Mayo Clin Proc. 2018;93:597.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Hellmich B, Flossmann O, Gross WL, et al. EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis. Ann Rheum Dis. 2007;66:605–17.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Hoffman GS. Immunosuppressive therapy is always required for the treatment of limited Wegener’s granulomatosis. Sarcoidosis Vasc Diffuse Lung Dis. 1996;13:249–52.PubMedPubMedCentralGoogle Scholar
  78. 78.
    Holle JU, Gross WL, Holl-Ulrich K, et al. Prospective long-term follow-up of patients with localised Wegener’s granulomatosis: does it occur as persistent disease stage? Ann Rheum Dis. 2010;69:1934–9.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Pagnoux C, Stubbe M, Lifermann F, et al. Wegener’s granulomatosis strictly and persistently localized to one organ is rare: assessment of 16 patients from the French Vasculitis Study Group database. J Rheumatol. 2011;38:475–8.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Cabral DA, Uribe AG, Benseler S, et al. Classification, presentation, and initial treatment of Wegener’s granulomatosis in childhood. Arthritis Rheum. 2009;60:3413–24.PubMedCrossRefGoogle Scholar
  81. 81.
    Akikusa JD, Schneider R, Harvey EA, et al. Clinical features and outcome of pediatric Wegener’s granulomatosis. Arthritis Rheum. 2007;57:837–44.PubMedCrossRefGoogle Scholar
  82. 82.
    Cabral DA, Canter DL, Muscal E, et al. Comparing presenting clinical features in 48 children with microscopic polyangiitis to 183 children who have granulomatosis with polyangiitis (Wegener’s): an ARChiVe cohort study. Arthritis Rheumatol. 2016;68:2514–26.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Morishita KA, Moorthy LN, Lubieniecka JM, et al. Early outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 2017;69:1470–9.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Iudici M, Pagnoux C, Quartier P, et al. Childhood- versus adult-onset ANCA-associated vasculitides: a nested, matched case-control study from the French Vasculitis Study Group Registry. Autoimmun Rev. 2018;17:108–14.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Koldingsnes W, Nossent JC. Baseline features and initial treatment as predictors of remission and relapse in Wegener’s granulomatosis. J Rheumatol. 2003;30:80–8.PubMedPubMedCentralGoogle Scholar
  86. 86.
    Karim AF, Verdijk RM, Nagtegaal AP, et al. To distinguish IgG4-related disease from seronegative granulomatosis with polyangiitis. Rheumatology (Oxford). 2017;56:2245–7.CrossRefGoogle Scholar
  87. 87.
    Bossuyt X, Cohen Tervaert JW, Arimura Y, et al. Position paper: revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis. Nat Rev Rheumatol. 2017;13:683–92.CrossRefGoogle Scholar
  88. 88.
    Mahr A, Batteux F, Tubiana S, et al. Brief report: prevalence of antineutrophil cytoplasmic antibodies in infective endocarditis. Arthritis Rheumatol. 2014;66:1672–7.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Duna GF, Galperin C, Hoffman GS. Wegener’s granulomatosis. Rheum Dis Clin North Am. 1995;21:949–86.PubMedPubMedCentralGoogle Scholar
  90. 90.
    Gluth MB, Shinners PA, Kasperbauer JL. Subglottic stenosis associated with Wegener’s granulomatosis. Laryngoscope. 2003;113:1304–7.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Gwathmey KG, Burns TM, Collins MP, Dyck PJ. Vasculitic neuropathies. Lancet Neurol. 2014;13:67–82.CrossRefGoogle Scholar
  92. 92.
    McGeoch L, Silecky WB, Maher J, Carette S, Pagnoux C. Temporal arteritis in the young. Joint Bone Spine. 2013;80:324–7.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Bourgarit A, Le Toumelin P, Pagnoux C, et al. Deaths occurring during the first year after treatment onset for polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: a retrospective analysis of causes and factors predictive of mortality based on 595 patients. Medicine (Baltimore). 2005;84:323–30.CrossRefGoogle Scholar
  94. 94.
    Faurschou M, Sorensen IJ, Mellemkjaer L, et al. Malignancies in Wegener’s granulomatosis: incidence and relation to cyclophosphamide therapy in a cohort of 293 patients. J Rheumatol. 2008;35:100–5.PubMedPubMedCentralGoogle Scholar
  95. 95.
    Flossmann O, Jayne DR. Long-term treatment of relapsing Wegener’s granulomatosis with 15-deoxyspergualin. Rheumatology (Oxford). 2010;49:556–62.CrossRefGoogle Scholar
  96. 96.
    Puechal X, Pagnoux C, Perrodeau E, et al. Long-Term Outcomes Among Participants in the WEGENT Trial of Remission-Maintenance Therapy for Granulomatosis With Polyangiitis (Wegener’s) or Microscopic Polyangiitis. Arthritis Rheumatol. 2016;68:690–701.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Jayne D, Rasmussen N, Andrassy K, et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. 2003;349:36–44.CrossRefGoogle Scholar
  98. 98.
    Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener’s granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med. 1983;98:76–85.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Pagnoux C, Guillevin L. Treatment of granulomatosis with polyangiitis (Wegener’s). Expert Rev Clin Immunol. 2015;11:339–48.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Walsh M, Merkel PA, Mahr A, Jayne D. Effects of duration of glucocorticoid therapy on relapse rate in antineutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis. Arthritis Care Res. 2010;62:1166–73.CrossRefGoogle Scholar
  101. 101.
    Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363:221–32.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    WGET. Etanercept plus standard therapy for Wegener’s granulomatosis. N Engl J Med. 2005;352:351–61.CrossRefGoogle Scholar
  103. 103.
    Guillevin L, Cordier JF, Lhote F, et al. A prospective, multicenter, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of generalized Wegener’s granulomatosis. Arthritis Rheum. 1997;40:2187–98.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    de Groot K, Harper L, Jayne DR, et al. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med. 2009;150:670–80.CrossRefGoogle Scholar
  105. 105.
    Lapraik C, Watts R, Bacon P, et al. BSR and BHPR guidelines for the management of adults with ANCA associated vasculitis. Rheumatology (Oxford). 2007;46:1615–6.CrossRefGoogle Scholar
  106. 106.
    Pagnoux C, Quemeneur T, Ninet J, et al. Treatment of systemic necrotizing vasculitides in patients aged sixty-five years or older: results of a multicenter, open-label, randomized controlled trial of corticosteroid and cyclophosphamide-based induction therapy. Arthritis Rheumatol. 2015;67:1117–27.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Monach PA, Arnold LM, Merkel PA. Incidence and prevention of bladder toxicity from cyclophosphamide in the treatment of rheumatic diseases: a data-driven review. Arthritis Rheum. 2010;62:9–21.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Pagnoux C, FVSG. Vascularites nécrosantes systémiques - protocole national de diagnostic et de soins. 2009. https://www.has-sante.fr.
  109. 109.
    Haubitz M, Schellong S, Gobel U, et al. Intravenous pulse administration of cyclophosphamide versus daily oral treatment in patients with antineutrophil cytoplasmic antibody-associated vasculitis and renal involvement: a prospective, randomized study. Arthritis Rheum. 1998;41:1835–44.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Harper L, Morgan MD, Walsh M, et al. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up. Ann Rheum Dis. 2012;71:955–60.CrossRefGoogle Scholar
  111. 111.
    Jones RB, Furuta S, Tervaert JW, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis: 2-year results of a randomised trial. Ann Rheum Dis. 2015;74:1178–82.PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Specks U, Merkel PA, Seo P, et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med. 2013;369:417–27.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Westwell-Roper C, Lubieniecka JM, Brown KL, et al. Clinical practice variation and need for pediatric-specific treatment guidelines among rheumatologists caring for children with ANCA-associated vasculitis: an international clinician survey. Pediatr Rheumatol Online J. 2017;15:61.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Holle JU, Dubrau C, Herlyn K, et al. Rituximab for refractory granulomatosis with polyangiitis (Wegener’s granulomatosis): comparison of efficacy in granulomatous versus vasculitic manifestations. Ann Rheum Dis. 2012;71:327–33.PubMedCrossRefPubMedCentralGoogle Scholar
  115. 115.
    Charles P, Bienvenu B, Bonnotte B, et al. Rituximab: recommendations of the French Vasculitis Study Group (FVSG) for induction and maintenance treatments of adult, antineutrophil cytoplasm antibody-associated necrotizing vasculitides. Presse Med. 2013;42:1317–30.PubMedCrossRefPubMedCentralGoogle Scholar
  116. 116.
    Cartin-Ceba R, Diaz-Caballero L, Al-Qadi MO, et al. Diffuse alveolar hemorrhage secondary to antineutrophil cytoplasmic antibody-associated vasculitis: predictors of respiratory failure and clinical outcomes. Arthritis Rheumatol. 2016;68:1467–76.CrossRefGoogle Scholar
  117. 117.
    Uechi E, Okada M, Fushimi K. Effect of plasma exchange on in-hospital mortality in patients with pulmonary hemorrhage secondary to antineutrophil cytoplasmic antibody-associated vasculitis: a propensity-matched analysis using a nationwide administrative database. PLoS One. 2018;13:e0196009.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Walsh M, Casian A, Flossmann O, et al. Long-term follow-up of patients with severe ANCA-associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear. Kidney Int. 2013;84:397–402.CrossRefGoogle Scholar
  119. 119.
    Walsh M, Catapano F, Szpirt W, et al. Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: a meta-analysis. Am J Kidney Dis. 2011;57:566–74.PubMedCrossRefPubMedCentralGoogle Scholar
  120. 120.
    Walsh M, Merkel PA, Peh CA, et al. Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial. Trials. 2013;14:73.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Pagnoux C, Mahr A, Hamidou MA, et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med. 2008;359:2790–803.CrossRefGoogle Scholar
  122. 122.
    Langford CA, Talar-Williams C, Barron KS, Sneller MC. A staged approach to the treatment of Wegener’s granulomatosis: induction of remission with glucocorticoids and daily cyclophosphamide switching to methotrexate for remission maintenance. Arthritis Rheum. 1999;42:2666–73.PubMedCrossRefPubMedCentralGoogle Scholar
  123. 123.
    Metzler C, Miehle N, Manger K, et al. Elevated relapse rate under oral methotrexate versus leflunomide for maintenance of remission in Wegener’s granulomatosis. Rheumatology (Oxford). 2007;46:1087–91.CrossRefGoogle Scholar
  124. 124.
    Hiemstra TF, Walsh M, Mahr A, et al. Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA. 2010;304:2381–8.CrossRefGoogle Scholar
  125. 125.
    Reinhold-Keller E, Fink CO, Herlyn K, Gross WL, De Groot K. High rate of renal relapse in 71 patients with Wegener’s granulomatosis under maintenance of remission with low-dose methotrexate. Arthritis Rheum. 2002;47:326–32.PubMedCrossRefPubMedCentralGoogle Scholar
  126. 126.
    Mahr A, Katsahian S, Varet H, et al. Revisiting the classification of clinical phenotypes of anti-neutrophil cytoplasmic antibody-associated vasculitis: a cluster analysis. Ann Rheum Dis. 2013;72:1003–10.PubMedCrossRefPubMedCentralGoogle Scholar
  127. 127.
    Karras A, Pagnoux C, Haubitz M, et al. Randomised controlled trial of prolonged treatment in the remission phase of ANCA-associated vasculitis. Ann Rheum Dis. 2017;76:1662–8.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Miloslavsky EM, Lu N, Unizony S, et al. Myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)-positive and ANCA-negative patients with granulomatosis with polyangiitis (Wegener’s): distinct patient subsets. Arthritis Rheumatol. 2016;68:2945–52.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Pagnoux C, Springer J. Editorial: classifying antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides according to ANCA type or phenotypic diagnosis: salt or pepper? Arthritis Rheumatol. 2016;68:2837–40.PubMedCrossRefGoogle Scholar
  130. 130.
    Schirmer JH, Wright MN, Herrmann K, et al. Myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)-positive granulomatosis with polyangiitis (Wegener’s) is a clinically distinct subset of ANCA-associated vasculitis: a retrospective analysis of 315 patients from a German vasculitis referral center. Arthritis Rheumatol. 2016;68:2953–63.PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    McGregor JG, Hogan SL, Hu Y, Jennette CE, Falk RJ, Nachman PH. Glucocorticoids and relapse and infection rates in anti-neutrophil cytoplasmic antibody disease. Clin J Am Soc Nephrol. 2012;7:240–7.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Cartin-Ceba R, Golbin JM, Keogh KA, et al. Rituximab for remission induction and maintenance in refractory granulomatosis with polyangiitis (Wegener’s): ten-year experience at a single center. Arthritis Rheum. 2012;64:3770–8.PubMedCrossRefPubMedCentralGoogle Scholar
  133. 133.
    Jones RB, Ferraro AJ, Chaudhry AN, et al. A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2009;60:2156–68.PubMedCrossRefPubMedCentralGoogle Scholar
  134. 134.
    Smith RM, Jones RB, Guerry MJ, et al. Rituximab for remission maintenance in relapsing antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2012;64:3760–9.CrossRefGoogle Scholar
  135. 135.
    Roubaud-Baudron C, Pagnoux C, Meaux-Ruault N, et al. Rituximab maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis. J Rheumatol. 2012;39:125–30.PubMedCrossRefGoogle Scholar
  136. 136.
    Alberici F, Smith RM, Jones RB, et al. Long-term follow-up of patients who received repeat-dose rituximab as maintenance therapy for ANCA-associated vasculitis. Rheumatology (Oxford). 2015;54:1153–60.CrossRefGoogle Scholar
  137. 137.
    Guillevin L, Pagnoux C, Karras A, et al. Rituximab versus Azathioprine for Maintenance in ANCA-Associated Vasculitis. N Engl J Med. 2014;371:1771–80.CrossRefGoogle Scholar
  138. 138.
    Gopaluni S, Smith RM, Lewin M, et al. Rituximab versus azathioprine as therapy for maintenance of remission for anti-neutrophil cytoplasm antibody-associated vasculitis (RITAZAREM): study protocol for a randomized controlled trial. Trials. 2017;18:112.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Charles P, Terrier B, Perrodeau E, et al. Comparison of individually tailored vs systematic rituximab regimens to maintain ANCA-associated vasculitis remissions: results of a prospective, randomized–controlled, phase 3 trial. Arthritis Rheumatol. 2017;69:Abst 2754.Google Scholar
  140. 140.
    Unizony S, Villarreal M, Miloslavsky EM, et al. Clinical outcomes of treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis based on ANCA type. Ann Rheum Dis. 2016;75:1166–9.CrossRefGoogle Scholar
  141. 141.
    Azar L, Springer J, Langford CA, Hoffman GS. Rituximab with or without a conventional maintenance agent in the treatment of relapsing granulomatosis with polyangiitis (Wegener’s): a retrospective single-center study. Arthritis Rheumatol. 2014;66:2862–70.PubMedCrossRefGoogle Scholar
  142. 142.
    de Groot K, Reinhold-Keller E, Tatsis E, et al. Therapy for the maintenance of remission in sixty-five patients with generalized Wegener’s granulomatosis. Methotrexate versus trimethoprim/sulfamethoxazole. Arthritis Rheum. 1996;39:2052–61.PubMedCrossRefPubMedCentralGoogle Scholar
  143. 143.
    Stegeman CA, Tervaert JW, de Jong PE, Kallenberg CG. Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener’s granulomatosis. Dutch Co-Trimoxazole Wegener Study Group. N Engl J Med. 1996;335:16–20.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Cohen Tervaert JW. Trimethoprim-sulfamethoxazole and antineutrophil cytoplasmic antibodies-associated vasculitis. Curr Opin Rheumatol. 2018;30:388.PubMedCrossRefPubMedCentralGoogle Scholar
  145. 145.
    Zycinska K, Wardyn KA, Zielonka TM, Krupa R, Lukas W. Co-trimoxazole and prevention of relapses of PR3-ANCA positive vasculitis with pulmonary involvement. Eur J Med Res. 2009;14(Suppl 4):265–7.PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Pagnoux C, Hogan SL, Chin H, et al. Predictors of treatment resistance and relapse in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis: comparison of two independent cohorts. Arthritis Rheum. 2008;58:2908–18.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Finkielman JD, Merkel PA, Schroeder D, et al. Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis. Ann Intern Med. 2007;147:611–9.PubMedCrossRefPubMedCentralGoogle Scholar
  148. 148.
    Kemna MJ, Damoiseaux J, Austen J, et al. ANCA as a predictor of relapse: useful in patients with renal involvement but not in patients with nonrenal disease. J Am Soc Nephrol. 2015;26:537–42.PubMedCrossRefPubMedCentralGoogle Scholar
  149. 149.
    Fussner LA, Hummel AM, Schroeder DR, et al. Factors determining the clinical utility of serial measurements of antineutrophil cytoplasmic antibodies targeting proteinase 3. Arthritis Rheumatol. 2016;68:1700–10.PubMedCrossRefPubMedCentralGoogle Scholar
  150. 150.
    Walsh M, Flossmann O, Berden A, et al. Risk factors for relapse of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2012;64:542–8.PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Stegeman CA. Anti-neutrophil cytoplasmic antibody (ANCA) levels directed against proteinase-3 and myeloperoxidase are helpful in predicting disease relapse in ANCA-associated small-vessel vasculitis. Nephrol Dial Transplant. 2002;17:2077–80.PubMedCrossRefPubMedCentralGoogle Scholar
  152. 152.
    de Groot K, Rasmussen N, Bacon PA, et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2005;52:2461–9.PubMedCrossRefPubMedCentralGoogle Scholar
  153. 153.
    Hu W, Liu C, Xie H, Chen H, Liu Z, Li L. Mycophenolate mofetil versus cyclophosphamide for inducing remission of ANCA vasculitis with moderate renal involvement. Nephrol Dial Transplant. 2008;23:1307–12.PubMedCrossRefPubMedCentralGoogle Scholar
  154. 154.
    Jayne DR, Chapel H, Adu D, et al. Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity. QJM. 2000;93:433–9.PubMedCrossRefPubMedCentralGoogle Scholar
  155. 155.
    Crickx E, Machelart I, Lazaro E, et al. Intravenous immunoglobulin as an immunomodulating agent in antineutrophil cytoplasmic antibody-associated vasculitides: a French nationwide study of ninety-two patients. Arthritis Rheumatol. 2016;68:702–12.PubMedCrossRefPubMedCentralGoogle Scholar
  156. 156.
    McAdoo SP, Bedi R, Tarzi R, Griffith M, Pusey CD, Cairns TD. Ofatumumab for B cell depletion therapy in ANCA-associated vasculitis: a single-centre case series. Rheumatology (Oxford). 2016;55:1437–42.CrossRefGoogle Scholar
  157. 157.
    Jayne DRW, Bruchfeld AN, Harper L, et al. Randomized trial of C5a receptor inhibitor avacopan in ANCA-associated vasculitis. J Am Soc Nephrol. 2017;28:2756–67.PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    Langford CA, Monach PA, Specks U, et al. An open-label trial of abatacept (CTLA4-Ig) in non-severe relapsing granulomatosis with polyangiitis (Wegener’s). Ann Rheum Dis. 2014;73:1376–9.PubMedCrossRefPubMedCentralGoogle Scholar
  159. 159.
    Jayne D, Blockmans D, Luqmani R, et al. Efficacy and Safety of Belimumab and Azathioprine for Maintenance of Remission in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Randomized Controlled Study. Arthritis Rheumatol. 2019;71:952–63.Google Scholar
  160. 160.
    Berti A, Cavalli G, Campochiaro C, et al. Interleukin-6 in ANCA-associated vasculitis: rationale for successful treatment with tocilizumab. Semin Arthritis Rheum. 2015;45:48–54.PubMedCrossRefPubMedCentralGoogle Scholar
  161. 161.
    Sakai R, Kondo T, Kikuchi J, et al. Corticosteroid-free treatment of tocilizumab monotherapy for microscopic polyangiitis: a single-arm, single-center, clinical trial. Mod Rheumatol. 2016;26:900–7.PubMedCrossRefPubMedCentralGoogle Scholar
  162. 162.
    Trial U-CC. Clinical trial of tocilizumab versus cyclophosphamide for microscopic polyangiitis and granulomatosis with polyangiitis. 01 May 2017 edn. UMIN-CTR Clinical Trial portal. 2018.Google Scholar
  163. 163.
    Kusunoki Y, Nakazawa D, Shida H, et al. Peptidylarginine deiminase inhibitor suppresses neutrophil extracellular trap formation and MPO-ANCA production. Front Immunol. 2016;7:227.PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    Nishide M, Nojima S, Ito D, et al. Semaphorin 4D inhibits neutrophil activation and is involved in the pathogenesis of neutrophil-mediated autoimmune vasculitis. Ann Rheum Dis. 2017;76:1440–8.PubMedPubMedCentralCrossRefGoogle Scholar
  165. 165.
    Booth A, Harper L, Hammad T, et al. Prospective study of TNF alpha blockade with infliximab in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. J Am Soc Nephrol. 2004;15:717–21.PubMedCrossRefGoogle Scholar
  166. 166.
    de Menthon M, Cohen P, Pagnoux C, et al. Infliximab or rituximab for refractory Wegener’s granulomatosis: long-term follow up. A prospective randomised multicentre study on 17 patients. Clin Exp Rheumatol. 2011;29:S63–71.PubMedPubMedCentralGoogle Scholar
  167. 167.
    Silva F, Seo P, Schroeder DR, et al. Solid malignancies among etanercept-treated patients with granulomatosis with polyangiitis (Wegener’s): long-term follow up of a multicenter longitudinal cohort. Arthritis Rheum. 2011;63:2495–503.PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Walsh M, Chaudhry A, Jayne D. Long-term follow-up of relapsing/refractory anti-neutrophil cytoplasm antibody associated vasculitis treated with the lymphocyte depleting antibody alemtuzumab (CAMPATH-1H). Ann Rheum Dis. 2008;67:1322–7.PubMedCrossRefPubMedCentralGoogle Scholar
  169. 169.
    Shen J, Gill J, Shangguan M, Sampaio MS, Bunnapradist S. Outcomes of renal transplantation in recipients with Wegener’s granulomatosis. Clin Transplant. 2011;25:380–7.PubMedCrossRefPubMedCentralGoogle Scholar
  170. 170.
    Avina-Zubieta JA, Mai A, Amiri N, et al. Risk of myocardial infarction and stroke in patients with granulomatosis with polyangiitis (Wegener’s): a population-based study. Arthritis Rheumatol. 2016;68:2752–9.PubMedCrossRefPubMedCentralGoogle Scholar
  171. 171.
    Tan JA, Dehghan N, Chen W, Xie H, Esdaile JM, Avina-Zubieta JA. Mortality in ANCA-associated vasculitis: a meta-analysis of observational studies. Ann Rheum Dis. 2017;76:1566–74.PubMedCrossRefPubMedCentralGoogle Scholar
  172. 172.
    Charlier C, Henegar C, Launay O, et al. Risk factors for major infections in Wegener granulomatosis: analysis of 113 patients. Ann Rheum Dis. 2009;68:658–63.PubMedCrossRefPubMedCentralGoogle Scholar
  173. 173.
    Kostianovsky A, Charles P, Alves JF, et al. Immunogenicity and safety of seasonal and 2009 pandemic A/H1N1 influenza vaccines for patients with autoimmune diseases: a prospective, monocentre trial on 199 patients. Clin Exp Rheumatol. 2012;30:S83–9.PubMedPubMedCentralGoogle Scholar
  174. 174.
    Pagnoux C, Mahendira D, Laskin CA. Fertility and pregnancy in vasculitis. Best Pract Res Clin Rheumatol. 2013;27:79–94.PubMedCrossRefPubMedCentralGoogle Scholar
  175. 175.
    Heijl C, Harper L, Flossmann O, et al. Incidence of malignancy in patients treated for antineutrophil cytoplasm antibody-associated vasculitis: follow-up data from European Vasculitis Study Group clinical trials. Ann Rheum Dis. 2011;70:1415–21.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Division of Rheumatology, Vasculitis ClinicMount Sinai HospitalTorontoCanada

Personalised recommendations